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Right arrow Cerebral protection

Ann Thorac Surg 2006;81:868-874
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Antegrade Cerebral Perfusion With a Simplified Technique: Unilateral Versus Bilateral Perfusion

Christian Olsson, MD * , Stefan Thelin, MD, PhD

Department of Surgical Sciences, Division of Cardiothoracic Surgery, Uppsala University Hospital, Uppsala, Sweden

Accepted for publication August 15, 2005.

* Address correspondence to Dr Olsson, Thoraxkliniken, Akademiska Sjukhuset, SE-751 85, Uppsala, Sweden (Email: christian.olsson{at}surgsci.uu.se).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: Selective antegrade cerebral perfusion has been introduced as a strategy of cerebral protection in operations on the aortic arch with hypothermic circulatory arrest. Several techniques of unilateral and bilateral cerebral perfusion have been described with varying results.

METHODS: Patients underwent either unilateral cerebral perfusion with a cannula in the right subclavian artery or bilateral cerebral perfusion, with an additional cannula in the left carotid artery. A simplified Seldinger-type technique for subclavian artery cannulation was employed. Results were analyzed with multivariable logistic regression analysis and propensity score analysis to adjust for nonrandomized treatment assignment.

RESULTS: Of 65 patients, 17 (26%) had unilateral cerebral perfusion. Mortality was 11% (n = 7); 14% (n = 9) had a stroke. In multivariable analysis, unilateral cerebral perfusion was significantly associated with stroke (odds ratio 6.6 [1.2 to 36]). Age more than 70 years was associated with in-hospital death (odds ratio 12 [1.3 to 113]), and concomitant coronary artery bypass graft surgery was associated with adverse outcome (odds ratio 23 [1.8 to 299]). Balancing variables in a propensity score analysis, stroke remained significantly more common with unilateral brain perfusion (29% versus 0%, p = 0.045). Complications associated with subclavian artery cannulation were encountered in 1 patient (1.5%).

CONCLUSIONS: The described cannulation technique is safe and effective. Bilateral cerebral perfusion is easily achieved and is associated with decreased stroke risk, and should be the preferred brain protection strategy.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
In operations involving the transverse aortic arch, acute or elective, circulatory arrest offers a bloodless, unobscured, accessible surgical field. To protect organs sensitive to ischemia (eg, brain, spinal cord, and kidneys), circulatory arrest is performed under deep hypothermia (hypothermic circulatory arrest [HCA]). Deep hypothermia has drawbacks and allows a limited period with assumed protection from end-organ damage [1–4]. To enhance protection of the brain, allowing an extended period under which surgical procedures on the arch can be performed safely, methods to perfuse the brain during HCA have been introduced [5–8]. Based on clinical and experimental work, retrograde cerebral perfusion (RCP) is now perhaps gradually being superseded by selective antegrade cerebral perfusion (SACP) [9–14]. Cannulation of the right subclavian or axillary artery, unlike alternative cannulation sites, provides a route for orthograde full flow bypass as well as SACP. The risks of visceral malperfusion, retrograde embolization, and extremity ischemia are greatly diminished and the need for cannula replacement obviated [15–19]. Several approaches to perfusion through the right subclavian (axillary) artery have been suggested, including unilateral SACP (without perfusion of the left carotid artery) [20, 21] and cannulation through an 8-mm Dacron graft anastomosed end-to-side to the artery to avoid the potential damage reported to occur with direct cannulation [21, 22].

In this study, a simple method for direct subclavian artery cannulation over a guidewire is described. Unilateral, right-sided SACP is compared with bilateral SACP (right subclavian artery plus left carotid artery), with in-hospital stroke and death as primary endpoints. Our hypothesis is that unilateral SACP is inferior to bilateral SACP in terms of increased risk of perioperative stroke or increased in-hospital mortality.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Acknowledgments
 References
 
Patients and Definitions
The study was approved after institutional review. Informed consent for the operation was obtained from all conscious patients. Patients undergoing operations on the proximal aorta with an open distal anastomosis during the period January 2001 to September 2004 using right subclavian artery cannulation and SACP (n = 65) were eligible for the study. Both unilateral and bilateral SACP were used throughout the study period. During the study period, another 17 patients undergoing similar operations without SACP (n = 2), with SACP by alternative routes (direct cannulation of one or more arch vessels, n = 10), or with RCP (n = 5) were not included. No patient fulfilling the inclusion criteria was excluded from further analysis.

Operations carried out within 24 hours of presentation were defined as acute, all other operations as elective. Death was defined as in-hospital death of any cause. Stroke was defined as a new focal or global neurologic deficit still present at discharge and in most cases confirmed with a computed tomography scan of the brain or specialist neurologic assessment, or both. Temporary neurologic deficit was defined as any new central neurologic deficit resolving spontaneously before discharge. Bleeding was defined as that requiring reexploration. Infection was defined as a wound infection requiring surgical reintervention.

Diagnostic, Anesthetic, and Operative Procedures
Definite diagnosis of aortic dissection or aneurysm was made with computed tomography. Elective patients underwent coronary angiography and transthoracic echocardiography preoperatively to assess left ventricular and valve function. In acute cases, echocardiography was performed in stable patients without risk of delayed transportation or surgery and depending on clinical indication. There were no attempts at targeted visualization of the subclavian artery specifically.

At operation, routine anesthetic procedures were employed. Monitoring included central venous pressure, bilateral radial artery pressure, 5-lead electrocardiography, nasopharyngeal temperature, intermittent arterial blood gas analysis, and continuous mixed venous saturation. In a majority of cases, cerebral saturation was monitored (INVOS 4100; Somanetics, Troy, Michigan). Standard roller-pump, nonpulsatile cardiopulmonary bypass (CPB) with a hollow-fiber oxygenator was used. Acid-base balance was managed by the {alpha}-stat method.

Median sternotomy was prepared by skin incision and hemostasis. A short (approximately 10 cm) transverse incision was made a few centimeters below the middle part of the right clavicle. The pectoralis major muscle fibers were spread and the fascia incised. Tributaries of the adjacent subclavian vein were ligated and divided if necessary. The artery was gently isolated; cervical nerve trunks were easily avoided. A small adventitial 5-0 pursestring suture was placed. After heparinization, the artery was punctured with a needle, and a guidewire introduced. The cannula (FemFlex II [18F to 20F]; Medtronic, Minneapolis, Minnesota) or elongated one-piece arterial cannula (EOPA [20F to 22F]; Edwards Lifesciences, Irvine, California) was forwarded on the guidewire, and after performing a small arteriotomy, was introduced into the artery a few centimeters and secured (Fig 1). The cannula was connected to the arterial line after deairing. At this point, it could be elected to commence CPB, in which case, a long two-stage right atrial cannula was introduced through either femoral vein. Then sternotomy was performed. Usually, right atrial cannulation with a standard two-stage venous return cannula was employed. The arch vessels were isolated. During cooling to moderately deep hypothermia (18°C to 22°C nasopharyngeal temperature), the aortic root was addressed. Cold blood cardioplegia was used for myocardial protection. The left side of the heart was vented through a right superior pulmonary vein catheter.


Figure 1
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  		Fig 1. (A) A pursestring suture (5-0 polypropylene) is placed anteriorly in the exposed subclavian artery. (B) A thin guidewire is introduced on which the cannula is advanced, and a small arteriotomy is made. (C) The cannula is introduced and secured. (D) Right complete set-up for bilateral selective antegrade cerebral perfusion. The arterial trunk is clamped proximally. A coronary sinus catheter is introduced in the snared left carotid artery.

 
On reaching target temperature, with the patient's head packed in ice, the circulation was arrested and the patient exsanguinated. The aortic cross-clamp was removed, and the aortic arch resected to the extent warranted by the disease. On clamping the innominate artery at its origin, SACP was begun at 250 to 500 mL/min. After controlling for contralateral backflow (also aiding deairing), the left carotid artery was cannulated under direct vision using a standard 15F coronary sinus cannula (DLP; Medtronic), joining the arterial line by a Y-connection. The SACP flow was then adjusted to 10 mL · kg–1 · min–1. A single roller-pump sufficed to deliver full-flow CPB as well as low-flow SACP without additional perfusion equipment. The left subclavian artery was not perfused; rarely was back bleeding considerable, warranting its temporary occlusion. On completion of the open distal anastomosis, with the patient in the Trendelenburg position, the left carotid cannula was clamped and removed, and SACP flow was down-regulated. Again, carotid artery backflow aided deairing of the anastomosis, as did removal of the innominate artery clamp. Full bypass was recommenced through the right subclavian cannula. During rewarming, additional procedures—for example, coronary artery grafting—were performed, and proximal and distal vascular grafts sutured together. After discontinuation of CPB and arterial decannulation, the subclavian arteriotomy was closed, primarily using the pursestring suture in all cases but 1.

Statistical Methods
Data were collected and stored in a database. Medical records were reviewed to include additional data. Variables are presented as integers with percentages or means with 95% confidence intervals (CI), if not stated otherwise. For group comparisons, Student's t test was used for continuous data, and the {chi}2 test or Fisher's exact test for dichotomized data. A two-tailed p value of less than 0.05 was considered statistically significant. The variables included in the statistical analyses are given in Table 1. Variables with p values less than 0.10 in bivariate analysis were included in forward multivariable logistic regression models to determine independent risk factors for the primary endpoints stroke and death and for the secondary composite endpoint adverse outcome, comprising death and stroke, as proposed by the Mount Sinai group [23, 24]. The resulting odds ratios are presented with 95% confidence intervals. Choice of perfusion strategy was surgeon-driven; patients were not randomly assigned. To adjust for possible selection bias, a propensity score based on all available, nonredundant preoperative variables was constructed [25, 26]. The variables were included in a logistic regression equation to calculate the propensity score for treatment received in each patient. Patients managed with unilateral SACP (n = 17) were matched with patients managed with bilateral SACP (n = 48) by constructing pairs with the closest propensity scores (greedy matching, from five digits to one digit). This way, a matched comparison, unbiased in known variables, with n = 17 in each group, was created. Variables producing zero patients in both groups were excluded from further analysis.


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  		Table 1. Characteristics of 65 Patients Undergoing Aortic Surgery With an Open Distal Anastomosis Using Selective Antegrade Cerebral Perfusion (SACP)
 

   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Acknowledgments
 References
 
During the study period, 65 patients underwent operations involving the aortic arch performed with SACP either unilaterally (right subclavian artery perfusion only, n = 17) or bilaterally (right subclavian artery and left carotid artery perfusion, n = 48). Mean age was 59 years (95% CI: 56 to 62). Seventy-five percent were men, 17% were 70 years or older, 62% underwent acute operations, and 12% were redos. Mean SACP time was 33 minutes (29 to 37; range, 15 to 81); in 26%, it exceeded 45 minutes. Seven patients died in hospital (11% [9.8% to 11.7%]). Nine patients (14% [12.8% to 14.9%]) had a stroke in the perioperative period. Three patients (4.6% [4.0% to 5.2%]) had temporary neurologic deficits (Table 1).

There were five intraoperative events related to subclavian artery cannulation. In 1 patient, the subclavian artery line was inadvertently clamped during SACP. In 1 patient, the subclavian artery was injured at cannulation and was reconstructed using an 8-mm Dacron graft at the conclusion of the operation. In 1 patient, the chosen cannula (24F EOPA) was found oversized and replaced by a smaller cannula (20F FemFlex II). In 2 patients, the cannula was dislodged and had to be reinserted or adjusted. Thus, in a single case (1.5%) was there clinically significant damage attributable to subclavian artery cannulation itself. No circulatory, neurologic, or infectious complications of the right arm were encountered.

In bivariate logistic regression analysis, two factors were related to stroke: EuroSCORE (European System for Cardiac Operative Risk Evaluation) greater than 8, indicating high risk (odds ratio [OR], 1.5); and unilateral SACP (OR, 6.6; Table 2). Age greater than 70 years was the single variable independently related to in-hospital death (OR, 12). All the variables related to adverse outcome in bivariate analysis (EuroSCORE greater than 8, acute operation, and occurrence of HCA without SACP) except for coronary artery bypass graft surgery were weakly related to adverse outcome in the multivariable model, including 1.0 in the 95% confidence interval of the odds ratio (Table 2). Coronary artery bypass graft surgery, however, was a stronger (OR, 23) independent predictor of adverse outcome. Patients with unilateral SACP more often underwent acute operations (Table 3), but this did not emerge as a risk factor for stroke, death, or adverse outcome. After matching based on propensity scores, differences in preoperative variables were overall better balanced (Table 3). In this analysis, stroke remained more common after unilateral SACP (5 of 17 versus 0 of 17, p = 0.045). In a multivariable model constructed identically, unilateral SACP was the only variable independently related to stroke in the propensity-score adjusted comparison (OR, 1.32 [1.02 to 1.71]).


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  		Table 2. Bivariate and Multivariable Risk Factor Analysis for Stroke, In-Hospital Death, and Adverse Outcome
 

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  		Table 3. Patients Managed With Unilateral and Bilateral Selective Antegrade Cerebral Perfusion (SACP) Before and After Propensity Score-Based Matching
 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Acknowledgments
 References
 
In aortic disease involving the transverse aortic arch, the choice of arterial cannulation site may influence outcome [15, 27]. Standard femoral artery cannulation, while providing relatively quick institution of CPB if necessary, is encumbered by several potential complications including false lumen perfusion in the dissected aorta, peripheral arterial disease, extremity ischemia, and embolization to the brain with the retrograde flow from the descending aorta [15–17, 27, 28]. Combining CPB on a femoral cannula with SACP requires the addition of separate cannulas for the arch vessels followed by, for example, graft cannulation to achieve orthograde flow after completion of the distal anastomosis. Although in some instances producing enviable results [12], a technique of separate cannulation of two or all three arch vessels seems cumbersome, involving repeated cannulation maneuvers and entailing counterproductive crowding of cannulas, monitoring lines, and clamps in the operative field. Again, there is a subsequent need for graft recannulation to institute orthograde CPB.

With subclavian artery cannulation, the single cannula needed for CPB and SACP is out of the way. It can be inserted before sternotomy, allowing safe mediastinal entrance on CPB in acute cases or redos. The SACP can be established by just occluding the innominate artery and reduce flow; bilateral SACP is easily achieved by inserting a cannula in the left carotid artery orifice under direct vision. Use of the more distal axillary and brachial parts of the artery has been described. At this level, the lumen diminishes, accommodating cannulas that cannot always provide full CPB flow, and the arm may need to be abducted to allow access [21]. The risk of perfusion-related complications using the axillary artery may be somewhat higher, 5.0% to 5.7% reported by Sabik and associates [18, 22], compared with 1.5% in this series.

We have found the right subclavian artery accessible for cannulation almost without exception, even in very obese patients (weighing as much as 140 kg). The excellent flow characteristics of the wire-reinforced cannulas allow the use of size 20F or smaller cannulas that are easily adapted to the surgical field remaining unkinked. This technique allows a smaller, flexible cannula and less arterial manipulation than the direct cannulation with a right-angled tip catheter [24]. It is simpler and faster than suturing a side graft to the artery, and it is not necessary to strangle the artery distally to the cannulation site to avoid hyperperfusion of the right arm [18, 22]. It avoids arteriotomy of the arch vessels that are often engaged by disease, be it dissection or atherosclerosis [10]. In our set-up, no separate roller-pumps are required for SACP, further simplifying its application.

Key points in the successful use of our method include (1) ensuring adequate back bleeding through the cannula, (2) avoiding oversized cannulas, (3) avoiding introduction of the cannula more than a few centimeters in the artery, and (4) ensuring that the artery is not unduly narrowed by tying the pursestring suture after decannulation. This method also includes monitoring the right radial artery pressure after decannulation. Potential drawbacks include the lack of arterial pressure monitoring in the right radial artery during CPB and the possibility of catheter dislodgement, as experienced in 2 cases in this series. With bilateral SACP, it is possible to monitor pressure in the left carotid artery cannula; we did not do this routinely, but when performed, the mean arterial pressure was invariably in the 40 to 70 mm Hg range with applied flows. Pressure monitoring might be of greater importance in unilateral SACP. In cases with known significant subclavian stenosis, we would avoid cannulating the artery, and we have not yet used the artery a second time for redo-cannulation with this technique.

Few other clinical studies have compared unilateral and bilateral SACP. Comparing crude outcomes (mortality, neurologic morbidity) in studies using either strategy, they would appear equal [21, 24]. But importantly, Dossche and colleagues [20], in a study of 106 patients undergoing operations on the proximal ascending aorta, found unilateral SACP (used in 35% of patients) associated with in-hospital death (overall mortality 8.5%; OR for death, 0.08, with bilateral SACP) and discouraged its use. In another study, flow velocity in the middle cerebral artery (examined by transcranial Doppler) was demonstrated to be significantly lower in the left cerebral hemisphere in unilateral SACP [29]. In this small study (n = 15), the diminished left-sided perfusion did not result in more adverse neurologic events. Perceivably, unilateral SACP is less physiologic than bilateral SACP, and depends on an intact and disease-free circle of Willis. The embolic challenge of a single high-flow cannula could be higher than with two cannulas balancing flow to the brain; and the margin of error could be narrowed, as exemplified by our 2 cases with cannula dislodgement and inadvertently clamped arterial line, respectively.

The 11% (9.8% to 11.7%) overall mortality is comparable to the 5% to 16.9% reported in the literature for similar patient groups [10, 13, 24]. Notably, this series comprised relatively large proportions of acute cases (more than 60%), and combined procedures (more than 20%). The majority of deaths (86%) were of patients managed with bilateral SACP. This difference, albeit not statistically significant, is notable and not easily understood. However, 100% of the redos and composite grafts were in the bilateral group, as well as 89% of the reexplorations for bleeding—one of several variables independently related to in-hospital death in multivariable analysis. Further, only 1 of these deaths is attributed to stroke, underscoring that death was unrelated to perfusion strategy. The 14% (12.8% to 14.9%) occurrence of perioperative stroke is on the high side [10, 13, 20–21]. Conversely, only 3 patients (4.6%) had transient neurologic deficits, for a total of 18.6% neurologic events. After bilateral SACP, 8% of patients suffered a stroke, compared with 29% after unilateral SACP (p = 0.045).

On radiologic examination (computed tomography), 4 of 6 patients with stroke after unilateral SACP had left-sided brain lesions; of them, 3 had bilateral lesions and 2 were watershed-type infarctions. Computed tomography was not performed in 1 patient. Of patients managed with bilateral SACP, all 3 patients had isolated right-sided lesions. The findings of left-sided infarctions in two thirds of unilateral SACP cases are compatible with left-sided underperfusion in unilateral SACP as it is performed in the right subclavian artery, depending on adequate collateral circulation to the contralateral side. However, in individual cases, a different etiology (air or particulate embolism, malperfusion) cannot be ruled out, and the incidence of preoperatively manifest or evolving cerebral infarctions was not known to us.

In the multivariable model, unilateral SACP was the single variable independently related to a permanent neurologic deficit, with an odds ratio of 6.6. Taking the nonrandomized assignment of treatment into account, a propensity score analysis was performed that lends further support to this finding: when patients are matched on all available variables in the propensity score, the groups are balanced and comparable. In this comparison, stroke was significantly more common among patients undergoing unilateral SACP, and remained the only independent predictor in a related multivariable model (OR, 1.32; Table 3). The SACP times were significantly longer in the bilateral group, but the HCA time, unperfused time (a period with HCA only, before establishment of or between periods of SACP), and the number of patients with a period of unperfused brain did not differ between groups, indicating overall similar conditions for cerebral perfusion in both groups.

Advanced age (older than 70 years) was the only independent risk factor for in-hospital death. Apart from protracted CPB time, no perfusion- or brain-protection–related variables influenced the risk of death in the models, reflecting the fact that only 1 death was due to stroke, whereas death in the other 6 cases were of other causes. Arguably, choice of perfusion strategy for cerebral protection may have less impact on perioperative mortality, in agreement with the findings of many others [13, 15, 30, 31]. In one study, however, perioperative stroke was an independent risk factor for in-hospital death [20]. For adverse outcome, coronary artery bypass graft surgery emerged as a strongly related independent variable, compared with several weakly related variables. Occurrence of periods of unperfused brain, namely, hypothermic circulatory arrest alone, was related to adverse outcome; this could reflect a higher complexity of arch reconstruction requiring temporary discontinuation of SACP. That could be of importance when circulatory arrest is established in the setting of moderate, rather than deep hypothermia. In the adverse outcome model, confidence intervals were generally very wide, rendering the results more difficult to interpret but suggesting that (expected) risk factors such as high operative risk (EuroSCORE) and acute operations carry increased risk for adverse outcome, but we do not regard these findings as conclusive.

The study is limited by its retrospective, nonrandomized design attempted to be counteracted by a propensity-score analysis. Several variables of potential importance for outcome, most notably preoperative cerebral damage in obtunded or intubated patients and various dissection-related complications, could not be analyzed. However, in the EuroSCORE, most variables of known importance to operative risk are included. Overall, the study findings support the hypothesis that a strategy of unilateral SACP is associated with an increased risk of perioperative cerebral damage.

Bilateral SACP is easily achieved with the reported technique, reducing manipulation with the arch vessels. Success rate is high, and complications rare. In this study, a strategy of bilateral SACP entailed fewer perioperative strokes than unilateral SACP, and unilateral SACP was the only variable independently associated with stroke. We suggest routine use of bilateral SACP for cases with a demanding open distal anastomosis.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
References
 
The study was financially supported by a grant from the Uppsala County Association Against Heart and Lung Diseases.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 

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Initial Experience of an Arterial Shunt for Bilateral Antegrade Cerebral Perfusion During Hypothermic Circulatory Arrest
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P. C. Austin
Propensity-score matching in the cardiovascular surgery literature from 2004 to 2006: a systematic review and suggestions for improvement.
J. Thorac. Cardiovasc. Surg., November 1, 2007; 134(5): 1128 - 1135.
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T. B. Reece, C. G. Tribble, R. L. Smith, R. R. Singh, B. M. Stiles, B. B. Peeler, J. A. Kern, and I. L. Kron
Central cannulation is safe in acute aortic dissection repair
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